Brain Connectivity Networks Constructed Using MRI for Predicting Patterns of Atrophy Progression in Parkinson Disease.

Background Whether connectome mapping of structural and functional connectivity across the brain could be used to predict patterns of atrophy progression in patients with mild Parkinson disease (PD) has not been well studied. Purpose To assess the structural and functional connectivity of brain regions in healthy controls and its relationship with the spread of gray matter (GM) atrophy in patients with mild PD. Materials and Methods This prospective study included participants with mild PD and controls recruited from a single center between January 2012 and December 2023. Participants with PD underwent three-dimensional T1-weighted brain MRI, and the extent of regional GM atrophy was determined at baseline and every year for 3 years. The structural and functional brain connectome was constructed using diffusion tensor imaging and resting-state functional MRI in healthy controls. Disease exposure (DE) indexes-indexes of the pathology of each brain region-were defined as a function of the structural or functional connectivity of all the connected regions in the healthy connectome and the severity of atrophy of the connected regions in participants with PD. Partial correlations were tested between structural and functional DE indexes of each GM region at 1- or 2-year follow-up and atrophy progression at 2- or 3-year follow-up. Prediction models of atrophy at 2- or 3-year follow-up were constructed using exhaustive feature selection. Results A total of 86 participants with mild PD (mean age at MRI, 60 years ± 8 [SD]; 48 male) and 60 healthy controls (mean age at MRI, 62 years ± 9; 31 female) were included. DE indexes at 1 and 2 years were correlated with atrophy at 2 and 3 years (r range, 0.22-0.33; P value range, .002-.04). Models including DE indexes predicted GM atrophy accumulation over 3 years in the right caudate nucleus and some frontal, parietal, and temporal brain regions (R2 range, 0.40-0.61; all P < .001). Conclusion The structural and functional organization of the brain connectome plays a role in atrophy progression in the early stages of PD. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Yamada in this issue.

Longitudinal brain connectivity changes and clinical evolution in Parkinson's disease.

Longitudinal connectivity studies might guide our understanding of the underlying neurodegenerative processes. We report the results of a longitudinal study in patients at different stages of Parkinson's disease (PD), who performed motor and non-motor evaluations and serial resting state (RS) functional MRI (fMRI). Cluster analysis was applied to demographic and clinical data of 146 PD patients to define disease subtypes. Brain network functional alterations were assessed at baseline in PD relative to 60 healthy controls and every year for a maximum of 4 years in PD groups. Progression of brain network changes were compared between patient clusters using RS fMRI. The contribution of network changes in predicting clinical deterioration was explored. Two main PD clusters were identified: mild PD (86 patients) and moderate-to-severe PD (60 patients), with the latter group being older and having earlier onset, longer PD duration, more severe motor, non-motor and cognitive deficits. Within the mild patient cluster, two clinical subtypes were further identified: mild motor-predominant (43) and mild-diffuse (43), with the latter being older and having more frequent non-motor symptoms. Longitudinal functional connectivity changes vary across patients in different disease stages with the coexistence of hypo- and hyper-connectivity in all subtypes. RS fMRI changes were associated with motor, cognitive and non-motor evolution in PD patients. Baseline RS fMRI presaged clinical and cognitive evolution. Our network perspective was able to define trajectories of functional architecture changes according to PD stages and prognosis. RS fMRI may be an early biomarker of PD motor and non-motor progression.

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.

Brain Structural Changes in Focal Dystonia-What About Task Specificity? A Multimodal MRI Study.

BACKGROUND: The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). METHODS: Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. RESULTS: The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. CONCLUSIONS: TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society.

Are there two different forms of functional dystonia? A multimodal brain structural MRI study.

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) - the typical fixed dystonia (FixFD) phenotype and the "mobile" dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels.

The Profile and Evolution of Neuropsychiatric Symptoms in Multiple System Atrophy: Self- and Caregiver Report.

OBJECTIVE: Recent research shows that patients with multiple system atrophy (MSA) have significant cognitive and neuropsychiatric comorbidities that can color the clinical presentation of the disease and affect their quality of life. The aims of this study were to determine the neuropsychiatric profile in a cohort of patients with the parkinsonian type of MSA (MSA-P) and their dynamic changes over a 1-year follow-up period and to compare rates of neuropsychiatric symptoms (NPSs) reported by caregivers and the patients themselves. METHODS: Forty-seven patients were assessed at baseline; of these, 25 were assessed again after 1 year. NPS assessment tools included the Neuropsychiatric Inventory (NPI), the Beck Depression Inventory, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Apathy Evaluation Scale. RESULTS: The prevalence of NPSs in patients with MSA-P was very high, with depression, sleep disturbances, apathy, and anxiety being the most frequently occurring features. The evolution of NPSs was found to be independent of motor, autonomic, and cognitive symptoms. None of the scales measuring NPSs, including the NPI, were capable of detecting changes over the 1-year follow-up period. Although the overall prevalence of depression, apathy, and anxiety obtained from caregivers and the patients themselves was similar, reports from these two sources cannot be considered interchangeable. CONCLUSIONS: The progression of neuropsychiatric symptoms was not a subject of rapid change in MSA-P, in contrast to the observed motor, autonomic, and cognitive deterioration. These findings suggest the need to investigate the utility of available instruments in capturing the evolution of NPSs in MSA over time.

Optical coherence tomography in patients with Wilson's disease.

OBJECTIVES: Wilson disease (WD) is an autosomal recessive disorder that leads to copper accumulation and deposition in different organs, frequently affecting visual pathways. Recent studies have detected morphological changes of the retina in patients with WD using optical coherence tomography (OCT). Measuring the thickness of the retinal nerve fibre layer (RNFL) with OCT provides an objective assessment of integrity and morphological abnormalities of the retina. The aim of this study was to evaluate the relationship between OCT parameters and form of the disease, therapy and symptoms duration, as well as severity of neurological impairment. METHODS: The study comprised of 52 patients with WD and 52 healthy controls (HC). All the patients were on a regular and stable chelation therapy and/or zinc salts. Patients were divided into two groups, with neurological (NWD) or hepatic form of the disease (HWD). OCT was performed to assess the RNFL thickness. RESULTS: The WD patients had significantly lower intraocular pressure in both eyes and lower RNFL thickness than the HC. There were no differences between NWD and HWD in any of the ophthalmologically tested parameters. No significant correlations were found between clinical features and retinal thickness parameters. Stratification of the cohort according to the disease duration showed that disease duration did not influence the RNFL thickness. CONCLUSION: We found that involvement of the retina represented a subclinical finding in neurologically intact patients in the HWD group. Nevertheless, the value of OCT as a biomarker for the assessment of the clinical course and progression of WD still remains uncertain.

Breakdown of the affective-cognitive network in functional dystonia.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.

Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease.

BACKGROUND: The objectives of this study were to investigate progressive cortical thinning and volume loss in Parkinson's disease (PD) patients with different longitudinal patterns of cognitive decline: with stable normal cognition, with stable mild cognitive impairment, with conversion to mild cognitive impairment, and with conversion to dementia. METHODS: We recruited 112 patients (37 Parkinson's disease with stable normal cognition, 20 Parkinson's disease with stable mild cognitive impairment, 36 Parkinson's disease with conversion to mild cognitive impairment, 19 Parkinson's disease with conversion to dementia) and 38 healthy controls. All patients underwent at least 2 visits within 4 years including clinical/cognitive assessments and structural MRI (total visits, 393). Baseline cortical thickness and gray matter volumetry were compared between groups. In PD, gray matter changes over time were investigated and compared between groups. RESULTS: At baseline, compared with Parkinson's disease with stable normal cognition cases, Parkinson's disease with conversion to mild cognitive impairment patients showed cortical atrophy of the parietal and occipital lobes, similar to Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia patients. The latter groups (ie, patients with cognitive impairment from the study entry) showed additional involvement of the frontotemporal cortices. No baseline volumetric differences among groups were detected. The longitudinal analysis (group-by-time interaction) showed that, versus the other patient groups, Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia cases accumulated the least cortical damage, with Parkinson's disease with conversion to dementia showing unique progression of right thalamic and hippocampal volume loss; Parkinson's disease with conversion to mild cognitive impairment patients showing specific cortical thinning accumulation in the medial and superior frontal gyri, inferior temporal, precuneus, posterior cingulum, and supramarginal gyri bilaterally; and Parkinson's disease with stable normal cognition patients showing cortical thinning progression, mainly in the occipital and parietal regions bilaterally. CONCLUSIONS: Cortical thinning progression is more prominent in the initial stages of PD cognitive decline. The involvement of frontotemporoparietal regions, the hippocampus, and the thalamus is associated with conversion to a more severe stage of cognitive impairment. In PD, gray matter alterations of critical brain regions may be an MRI signature for the identification of patients at risk of developing dementia. © 2020 International Parkinson and Movement Disorder Society.

Change in fear of falling in Parkinson's disease: a two-year prospective cohort study.

ABSTRACTBackground:Fear of falling in Parkinson's disease (PD) has been suggested as predictor of future falling. The purpose of this study was to compare fear of falling score after two years of follow-up with those observed at baseline and to assess factors associated with change in fear of falling over time. METHODS: A total of 120 consecutive persons with PD were recruited and followed for two years. Fear of falling was assessed by using the 10-item Falls Efficacy Scale (FES). Occurrence of falling was registered during the first year of follow-up. RESULTS: After two years, the average FES score statistically significantly changed (p = 0.003) from 30.5 to 37.5 out of 100 (increase of 22.9%). We observed that median scores of all FES items, except for "Preparing a meal, not requiring carrying of heavy or hot objects" and "Personal grooming," significantly increased after two-year follow-up. After accounting for age, gender, PD duration, levodopa dosage, Hoehn and Yayhr stage, Unified Parkinson's Disease Rating Scale score three, depression, anxiety, and falling, we observed that sustaining greater number of falls in the first year of follow-up was associated with higher increase in FES score after two years (odds ratio 3.08, 95% confidence interval 1.30-4.87). CONCLUSION: After two years of follow-up, we observed a decrease in confidence at performing nearly all basic daily activities. Fall prevention programs should be prioritized in management of PD.

Use of the Neuropsychiatric Inventory to Characterize the Course of Neuropsychiatric Symptoms in Progressive Supranuclear Palsy.

The aim of this study was to determine the neuropsychiatric profile in a cohort of progressive supranucelar palsy (PSP) patients and their dynamic changes over a follow-up period of 1 year. A total of 59 patients were assessed at baseline, while 25 of them were accessible after 1 year of the follow-up. The most common symptoms were apathy and depression, which were also found to be, among other variables, the independent determinants of increased Neuropsychiatric Inventory (NPI) total score. Moreover, apathy deteriorated most profoundly over the follow-up period. The NPI seemed to be a sensitive measure of behavioral changes in PSP.

Dynamics of change in self-reported disability among persons with Parkinson's disease after 2 years of follow-up.

Symptoms of Parkinson's disease (PD) progress over time causing significant disability. Yet, change in disability over shorter time periods has not been entirely understood. The purpose of this study was to assess the Self-Assessment Disability Scale (SADS) in persons with Parkinson's disease (PD) after 2 years of follow-up and compare it with the score observed at baseline. Additionally, we aimed at evaluating association of motor and non-motor PD features at baseline with a higher disability after 2 years of follow-up. A total of 120 consecutive persons with PD, who denied falling in the past 6 months, were initially recruited. After 2 years of follow-up, 88 (73.3%) persons with PD were evaluated for SADS. The total disability (SADS) score did not change after follow-up (p = 0.529). We observed increase in difficulty at "Getting out of bed" (p = 0.006), "Getting up out of armchair" (p = 0.013), "Walking about house/flat" (p = 0.003), "Walking outside" (p = 0.010), and "Traveling by public transport" (p = 0.014). After adjusting for several potential confounding factors, falls in the past year (ß = 8.32, 95% confidence interval (CI) 1.04-15.59) and higher Unified Parkinson's Disease Rating Scale part 3 at baseline (ß = 0.26, 95%CI 0.01-0.51) remained associated with higher PD-related disability. This finding suggests that accumulation of overall PD-related disability tends to occur over a longer time span. Further studies are needed to gradually assess long-term evolution of disability in PD.

Psychiatric Symptoms in the Initial Motor Stage of Parkinson's Disease.

Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD). The aim of this study was to estimate the correlates of NPS in patients with PD in the initial motor stage of the disease (hemiparkinsonism). A total of 111 patients with PD and 105 healthy control participants were assessed. Patients with PD experienced apathy, depression, and anxiety more frequently compared with healthy controls. Sleep disturbances occurred commonly in early PD patients. Patients with PD and mild cognitive impairment (MCI) had depression and anxiety more frequently, but not apathy, compared with patients with PD without MCI. The results of this study confirm a high burden of NPS even in the earliest motor stage of PD.

Indoor and outdoor falls in persons with Parkinson's disease after 1 year follow-up study: differences and consequences.

Falls among persons with Parkinson's disease (PD) often result in activity limitations, participation restrictions, social isolation or premature mortality. The purpose of this 1-year follow-up study was to compare potential differences in features of PD attributing to falls in relation to fall location (outdoor vs. indoor). We recruited 120 consecutive persons with PD who denied having fallen in the past 6 months. Disease stage and severity was assessed using the Hoehn and Yahr scale and the newer version of the Unified Parkinson's Disease Rating Scale. Occurrence of falling and characteristics of falls was followed for 1 year. Results were assessed statistically. Outdoor falls were more commonly preceded by the extrinsic factors (tripping and slipping). Slipping was more common outdoors (p = 0.001). Indoor falls were mostly preceded by the intrinsic factors (postural instability, lower extremity weakness, vertigo). Vertigo was more common indoors (p = 0.006). Occurrence of injuries was more common after outdoor falls (p = 0.001). Indoor falls resulted in contusions only, while outdoor falls resulted in lacerations and fractures as well. In the regression model adjusted for age, disease duration, on/off phase during fall, Hoehn and Yahr stage of disease and levodopa dosage, slipping was associated with outdoor falling (odds ratio = 17.25, 95 % confidence interval 3.33-89.20, p = 0.001). These findings could be used to tailor fall prevention program with emphasis on balance recovery and negotiation of objects in environment.

Modeling the BOD of Danube River in Serbia using spatial, temporal, and input variables optimized artificial neural network models.

This paper describes the application of artificial neural network models for the prediction of biological oxygen demand (BOD) levels in the Danube River. Eighteen regularly monitored water quality parameters at 17 stations on the river stretch passing through Serbia were used as input variables. The optimization of the model was performed in three consecutive steps: firstly, the spatial influence of a monitoring station was examined; secondly, the monitoring period necessary to reach satisfactory performance was determined; and lastly, correlation analysis was applied to evaluate the relationship among water quality parameters. Root-mean-square error (RMSE) was used to evaluate model performance in the first two steps, whereas in the last step, multiple statistical indicators of performance were utilized. As a result, two optimized models were developed, a general regression neural network model (labeled GRNN-1) that covers the monitoring stations from the Danube inflow to the city of Novi Sad and a GRNN model (labeled GRNN-2) that covers the stations from the city of Novi Sad to the border with Romania. Both models demonstrated good agreement between the predicted and actually observed BOD values.

Health-related quality of life as a predictor of recurrent falling in Parkinson's disease: 1-year follow-up study.

OBJECTIVE: The aim of this study was to assess whether various domains related to health-related quality of life could be predictive of recurrent falls among persons with Parkinson's disease (PD) during a 1-year follow-up study. METHODS: A total of 120 consecutive persons with PD who had denied falling in past 6 months were recruited at regular check-ups at the Department of Movement Disorders, Neurology Clinic, Clinical Center of Serbia in Belgrade, from 15 August 2011 to 15 December 2012. At baseline, study participants were clinically assessed. Health-related quality of life was evaluated with the generic 36-item Short Form Health Survey. Participants were prospectively followed for 1 year, and occurrence of falls was registered. RESULTS: The median age of subjects was 60.0 years, with a median disease duration of 4.0 years. Of 120 persons with PD, 42 (35%) experienced falls during the 12-month study period, including 23 (19.2%) who fell repeatedly. After adjustment for gender, age, PD duration, levodopa dosage, Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale I-IV, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scales, we identified the 36-item Short Form Health Survey domains of role physical (P = 0.033) and vitality (P = 0.019) as being associated with recurrent falls of persons with PD within the 1-year follow-up period. CONCLUSION: Baseline 36-item Short Form Health Survey scores regarding both the physical and mental components of overall health may be related to recurrent falling among persons with PD. These HRQoL domains could be considered as potential markers for persons with PD who are prone to recurrent falls.

Mild Cognitive Impairment in Early Parkinson's Disease Using the Movement Disorder Society Task Force Criteria: Cross-Sectional Study in Hoehn and Yahr Stage 1.

BACKGROUND: Mild cognitive impairment (MCI) in Parkinson's disease (PD) is common and confers a higher risk for developing dementia. METHODS: In this cross-sectional study of MCI in PD conducted at a university hospital, a comprehensive neuropsychological battery covering five domains (attention/working memory, executive, verbal, and visual memory, language, and visuospatial) was administered to 111 nondemented PD patients in Hoehn and Yahr stage 1 and to 105 healthy matched control subjects (HC). MCI was diagnosed according to level 2 of the Movement Disorder Society Task Force criteria. RESULTS: Criteria for MCI associated with PD (PD-MCI) were fulfilled by 24% of PD patients in the initial stage of the disease at the z cutoff scores of -1.5 SD in contrast to 7% of HC fulfilling criteria for MCI. Memory and visuospatial domains were the most commonly affected at -1.5 SD. PD-MCI patients mostly had a multiple-domain MCI subtype (78%). They presented a more severe bradykinesia and higher mood and apathy scores in comparison with cognitively normal PD patients. Basic motor scores predicted performance on some cognitive tests and specific cognitive-motor relationships emerged. CONCLUSIONS: MCI, predominantly of a multiple-domain subtype, was quite prevalent even in the initial stage of PD.

Mild cognitive impairment in Parkinson's disease is associated with a distributed pattern of brain white matter damage.

This study assesses the patterns of gray matter (GM) and white matter (WM) damage in patients with Parkinson's disease and mild cognitive impairment (PD-MCI) compared with healthy controls and cognitively unimpaired PD patients (PD-Cu). Three-dimensional T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were obtained from 43 PD patients and 33 healthy controls. Cognition was assessed using a neuropsychological battery. Tract-based spatial statistics was applied to compare DT MRI indices between groups on a voxel-by-voxel basis. Voxel-based morphometry was performed to assess GM atrophy. Thirty PD patients were classified as MCI. Compared with healthy controls, PD-Cu and PD-MCI patients did not have GM atrophy. No region of WM damage was found in PD-Cu patients when compared with healthy controls. Relative to healthy controls and PD-Cu patients, PD-MCI patients showed a distributed pattern of WM abnormalities in the anterior and superior corona radiata, genu, and body of the corpus callosum, and anterior inferior fronto-occipital, uncinate, and superior longitudinal fasciculi, bilaterally. Subtle cognitive decline in PD is associated with abnormalities of frontal and interhemispheric WM connections, and not with GM atrophy. DT MRI might contribute to the identification of structural changes in PD-MCI patients prior to the development of dementia.